Air pollution has been linked to a range of ill health effects, including cardiovascular, neurological, and respiratory morbidity. In particular, epidemiologic evidence linking particulate matter (PM) and worse pulmonary outcomes in subjects with asthma has been well described. In vitro, animal, and human challenge experiments have also suggested mechanistic associations between PM exposure and markers of inflammation and oxidative stress. However, a causal relationship between pollutant exposure and asthma morbidity has not yet been established. Moreover, there is a lack of evidence regarding the impact of deliberately decreasing exposures on asthma health that could help inform clinical guidelines and public policies. Fortunately, there is precedence in our research group at the Center for Childhood Asthma in the Urban Environment (CCAUE) that improving indoor air quality in homes can be achieved relatively simply, resulting in improved respiratory symptoms. In this application, we plan to investigate the potential mechanisms whereby reducing pollutant exposure may improve asthma morbidity. The aim is to study 35 asthmatics with high levels of indoor pollution before and after a 6 month-long intervention that places air cleaners in the home. Biological processes such as inflammation, oxidative stress, and epithelial barrier dysfunction will be assessed for signs of amelioration after pollution abatement. Specifically, biomarkers from bronchoscopic samples, exhaled breath, blood and urine known to be altered in people with asthma will be measured after exposure to pollution. In addition, clinical measures of improved asthma morbidity such as decreased symptoms and improved physiologic measures (i.e. lung function and bronchial hyperreactivity) will be assessed before and after the intervention. Ultimately, the information from this application will contribute to the understanding of mechanisms underlying improvement of asthma morbidity when exposed to cleaner air in the indoor environment. Additionally, if full or partial reversal of pathology can be demonstrated by reducing indoor PM, it will strengthen a causal relationship between PM and asthma morbidity that would support public policy actions aimed at improving respiratory health. The data generated from this research proposal will form the basis for an R01 application. The career development plan for this applicant includes a structured approach to mentoring, didactic coursework focused on a specific research goal, participation in local and national meetings and identification and regular assessment of career milestones. The research environment provided by Johns Hopkins University as well as the mentorship team outlined in this application will assist in a successful completion of the candidate's career and research goals. The Division of Pulmonary and Critical Care Medicine and Johns Hopkins University have a long history of training successful clinical researchers in a supportive and collaborative environment. The pre-existing structure of the Center for Childhood Asthma in the Urban Environment (CCAUE), a collaborative, multidisciplinary research group that has been conducting asthma research in Baltimore for several years, will provide the infrastructure and resources needed to ensure that study procedures will be completed within the timeframe of this award. A mentoring team has been assembled of established faculty with many years of productive research experience and substantial prior mentoring experience. Each has distinct, complementary strengths in areas of research relevant to this proposal. In addition, each member of the mentoring committee serves as an excellent role model for the applicant's career development into an independent investigator. PUBLIC HEALTH RELEVANCE: This project seeks to understand the various ways that reducing air pollution inside the home leads to improvement in symptoms in people with asthma. The investigators will determine the effects of an air cleaner upon biological processes and clinical features that are characteristic to asthma. Ultimately, these studies should help physicians and policy makers decide how and why reducing indoor pollution reduces illness among those with asthma.